DNA nanotechnology enables the bottom-up construction of membrane nanopores with programmable geometry and function. This chapter surveys design strategies for synthetic DNA nanopores, from DNA-origami pores with barrel-stem architectures to multi-helix bundles (e.g., 6HB) and minimal bundles (4HB) or membrane-spanning duplexes, and outlines how these structures are embedded in lipid bilayers despite DNA’s hydrophilicity and negative charge. We highlight how hydrophobic anchoring (e.g., cholesterol), membrane curvature, and surfactants govern insertion yields and aggregation behavior, providing practical routes to robust reconstitution in vesicles. Functionally, DNA nanopores mediate size- and charge-selective transport of small dyes and large molecules (over several tens of kDa) depending on their design, while tunable “gates” respond to DNA inputs, temperature, or light to realize reversible open–close control. Combining pores with DNA reaction networks inside vesicles further enables reception-transduction-response cascades as an artificial molecular system. We conclude by outlining open challenges, such as ion selectivity, active transport against gradients, and cargo selectivity, and discuss the potential for advancement toward "Chemical AI" based on synthetic DNA nanopores.

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Synthetic DNA Nanopore

  • En Kawakubo,
  • Towa Higashiho,
  • Yusuke Sato

摘要

DNA nanotechnology enables the bottom-up construction of membrane nanopores with programmable geometry and function. This chapter surveys design strategies for synthetic DNA nanopores, from DNA-origami pores with barrel-stem architectures to multi-helix bundles (e.g., 6HB) and minimal bundles (4HB) or membrane-spanning duplexes, and outlines how these structures are embedded in lipid bilayers despite DNA’s hydrophilicity and negative charge. We highlight how hydrophobic anchoring (e.g., cholesterol), membrane curvature, and surfactants govern insertion yields and aggregation behavior, providing practical routes to robust reconstitution in vesicles. Functionally, DNA nanopores mediate size- and charge-selective transport of small dyes and large molecules (over several tens of kDa) depending on their design, while tunable “gates” respond to DNA inputs, temperature, or light to realize reversible open–close control. Combining pores with DNA reaction networks inside vesicles further enables reception-transduction-response cascades as an artificial molecular system. We conclude by outlining open challenges, such as ion selectivity, active transport against gradients, and cargo selectivity, and discuss the potential for advancement toward "Chemical AI" based on synthetic DNA nanopores.